TPL-2/Cot and Cox-2 in Breast Cancer

Abstract

Background: Breast cancer is the most common cancer in women worldwide and although mortality (129 000/year) stagnates, incidence (370 000/year) is increasing. In addition to histological type, grade, stage, hormonal and c-erbB2 status there is therefore a strong need for new and reliable prognostic and predictive factors.Methods and results: This minireview focuses on two potential prognostic and predictive candidates Tpl2/Cot and COX-2 and summarise information about them.Conclusion: Tumor progression locus 2 (Tpl2/Cot) is a serine/threonine protein kinase belonging to the family of MAP3 kinases. Activated Tpl2/Cot leads to induction of ERK1/2, JNK, NF-κB and p38MAPK pathways. The fi rst study on Tpl2/Cot mRNA in breast cancer showed its increase in 40 % of cases of breast cancer but no available data exist on protein expression. Cyclo-oxygenase 2 (COX-2) is inducible by growth and infl ammatory factors and contributes to the development of various tumours. Expression of COX-2 in breast cancer varied from 5-100 % in reviewed papers with signifi cantly higher values in poorly diff erentiated tumours. Tpl2/Cot and COX-2 have their importance in diff erent intracellular pathways and some of these are involved in cancer development. Briefl y, the results from recent studies suggest that Tpl2/Cot and COX-2 could be prognostic factors in breast cancer.

Tpl2 regulates intestinal myofibroblast HGF release to suppress colitis-associated tumorigenesis

“…**P < 0.01. (21,23,24), there is evidence that it may act as a tumor suppressor, as shown in Tpl2-deficient mice developing enhanced lymphomas in the MHC class I-restricted T cell antigen receptor (TCR) transgenic background (25) and a higher number and incidence of chemically induced skin tumors (26). So far, there is very little evidence on the role of the Tpl2 kinase in intestinal inflammation and carcinogenesis.…”

Inhibition of metadherin sensitizes breast cancer cells to AZD6244

“…1,2 Despite the recent advances made in breast cancer treatment utilizing improved local and systemic treatments to improve disease-free and overall survival in the general female breast cancer population, about one-third of patients diagnosed with early-stage breast cancer eventually die of recurrent disease due to the development of drug resistance to systemic therapy. 3,4 The specific nature in which certain breast cancers develop chemotherapy resistance, the biologic mechanisms of action, and the role of genes involved in the transport of anticancer agents that lead to resistance remain unclear.…”

Review of Soybean Phytochemicals and Their Bioactive Properties Relevant for Skin Health

“…Furthermore, another metabolite, 7.3',4'-THIF has been proposed as an inhibitor of Cot and MKK4 in a UVB-induced skin inflammation model [44]. Cot and MKK4 are inflammatory signaling proteins that regulate MAPK phosphorylation [45,46]. The kinase activity of Cot and MKK4 were both significantly attenuated with 7,3',4'-THIF treatment, whereas p38a JNK1, ERKs, and MSK1 activities remained unaffected.…”